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Introduction: Severe acute pancreatitis (AP) requiring critical care admission (ccAP) impacts negatively on long-term survival. Objective: To document organ-specific new morbidity and identify risk factors associated with premature mortality after an episode of ccAP.Design: Cohort studySetting: Electronic healthcare registries in Scotland.Participants: ccAP cohort: 1471 patients admitted to critical care with AP between 1st January 2008 and 31st December 2010 followed up until 31st December 2014; population cohort: 3450 individuals from the general population of Scotland frequency matched for age, sex and social deprivation.Methods: Record linkage of routinely-collected electronic health data with population matching.Primary and secondary outcome measures: Patient demographics, co-morbidity (Charlson Index), acute physiology, organ support and other critical care data were linked to records of mortality (death certificate data) and new-onset morbidity. Kaplan Meier and Cox regression analyses were used to identify risk factors associated with mortality. Results: 310 patients with AP died during the index admission. Outcomes were not ascertained for 5 patients, and the deprivation quintile was not known for 6 patients. 340 of 1150 patients in the resulting post-discharge ccAP cohort died during the follow-up period. Greater co-morbidity measured by the Charlson score, prior to ccAP, negatively influenced survival in hospital and after discharge. The odds of developing new-onset diabetes mellitus after ccAP compared to the general population was 10.70 (95% C.I. 5.74 to 19.94). A new diagnosis of myocardial infarction, stroke, heart failure, liver disease, peptic ulcer, renal failure, cancer, peripheral vascular disease and lung disease was more frequent in the ccAP cohort than the general population.Conclusions: The persistent deleterious impact of severe AP on long-term outcome and survival is multifactorial in origin, influenced by pre-existing patient characteristics and acute episode features. Further mechanistic and epidemiologic investigation is warranted.

This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1 . STUDY QUESTION What is the impact of cancer in females aged ≤39 years on subsequent chance of pregnancy? SUMMARY ANSWER Cancer survivors achieved fewer pregnancies across all cancer types, and the chance of achieving a first pregnancy was also lower. WHAT IS KNOWN ALREADY The diagnosis and treatment of cancer in young females may be associated with reduced fertility but the true pregnancy deficit in a population is unknown. STUDY DESIGN, SIZE, DURATION We performed a retrospective cohort study relating first incident cancer diagnosed between 1981 and 2012 to subsequent pregnancy in all female patients in Scotland aged 39 years or less at cancer diagnosis (n = 23 201). Pregnancies were included up to end of 2014. Females from the exposed group not pregnant before cancer diagnosis (n = 10 271) were compared with general population controls matched for age, deprivation quintile and year of diagnosis. PARTICIPANTS/MATERIALS, SETTING, METHODS Scottish Cancer Registry records were linked to hospital discharge records to calculate standardized incidence ratios (SIR) for pregnancy, standardized for age and year of diagnosis. Linkage to death records was also performed. We also selected women from the exposed group who had not been pregnant prior to their cancer diagnosis who were compared with a matched control group from the general population. Additional analyses were performed for breast cancer, Hodgkin lymphoma, leukaemia, cervical cancer and brain/CNS cancers. MAIN RESULTS AND THE ROLE OF CHANCE Cancer survivors achieved fewer pregnancies: SIR 0.62 (95% CI: 0.60, 0.63). Reduced SIR was observed for all cancer types. The chance of achieving a first pregnancy was also lower, adjusted hazard ratio = 0.57 (95% CI: 0.53, 0.61) for women >5 years after diagnosis, with marked reductions in women with breast, cervical and brain/CNS tumours, and leukaemia. The effect was reduced with more recent treatment period overall and in cervical cancer, breast cancer and Hodgkin lymphoma, but was unchanged for leukaemia or brain/CNS cancers. The proportion of pregnancies that ended in termination was lower after a cancer diagnosis, and the proportion ending in live birth was higher (78.7 vs 75.6%, CI of difference: 1.1, 5.0). LIMITATIONS, REASONS FOR CAUTION Details of treatments received were not available, so the impact of specific treatment regimens on fertility could not be assessed. Limited duration of follow-up was available for women diagnosed in the most recent time period. WIDER IMPLICATIONS OF THE FINDINGS This analysis provides population-based quantification by cancer type of the effect of cancer and its treatment on subsequent pregnancy across the reproductive age range, and how this has changed in recent decades. The demonstration of a reduced chance of pregnancy across all cancer types and the changing impact in some but not other common cancers highlights the need for appropriate fertility counselling of all females of reproductive age at diagnosis. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by NHS Lothian Cancer and Leukaemia Endowments Fund. Part of this work was undertaken in the MRC Centre for Reproductive Health which is funded by the MRC Centre grant MR/N022556/1. RAA has participated in Advisory Boards and/or received speaker’s fees from Beckman Coulter, IBSA, Merck and Roche Diagnostics. He has received research support from Roche Diagnostics, Ansh labs and Ferring. The other authors have no conflicts to declare. Publisher PDF